TMEM-MRI: A Pilot Feasibility Study of MRI for Imaging of TMEM in Patients With Operable Breast Cancer (TMEM-MRI)

November 5, 2025 updated by: Montefiore Medical Center

TMEM-MRI: A Pilot Feasibility Study of Magnetic Resonance Imaging for Imaging of TMEM (Tumor Microenvironment of Metastasis) in Patients With Operable Breast Cancer

The aim of this study is to assess feasibility of a new imaging technology in the management of breast cancer - Tumor Microenvironment of Metastasis - Magnetic Resonance imaging (TMEM-MRI).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The primary objective of this study is to develop a magnetic resonance imaging (MRI) based method for assessing TMEM-mediated permeability associated with cancer cell dissemination in breast cancer patients. TMEM-MRI has the ability to detect tumor areas with more leakiness (perfusion), where cancer cells enter blood vessels to travel to other sites. This novel TMEM-MRI has potential to be used in clinical practice to identify tumors with high leakiness that might have higher chances to recur after breast cancer treatment. In addition, TMEM-MRI can potentially be used to assess response to preoperative treatments (chemotherapy, hormonal therapy) over time.

In a prior study, it was found that patients with high TMEM doorway score, compared to patients with mid/low TMEM doorway score, in their residual disease after neoadjuvant therapy, had worse distant relapse-free survival (p = 0.008). These results demonstrated that TMEM doorway density after neoadjuvant therapy is a prognostic biomarker of breast cancer outcomes. In the initial development of the proposed TMEM MRI in humans, the tumor microenvironment is naïve to treatment. However, neoadjuvant therapy may affect the tumor microenvironment which could affect vascular anatomy - a key component of the TMEM MRI algorithm. Therefore, the study team aims to assess the correlation between TMEM doorway density and TMEM MRI activity after neoadjuvant therapy (Pilot Cohort C).

Study Type

Interventional

Enrollment (Estimated)

95

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • New York
      • The Bronx, New York, United States, 10461
        • Recruiting
        • Montefiore Medical Center
        • Principal Investigator:
          • Jesus Anampa, MD
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Della Makower, MD
        • Sub-Investigator:
          • Sun Young Oh, MD
        • Sub-Investigator:
          • Maureen McEvoy, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria

  • For pre-pilot phase (MRI sequence development):

    o Patients with a breast mass, with biopsy-proven histology of invasive breast carcinoma (any histologic type and ER,PR,HER2 status)

  • For pilot phase Cohort A:

    o Patients with a breast mass considered highly suspicious for invasive carcinoma by the radiologist (BIRADS 5).

  • For pilot phase Cohort B:

    • Patients with a breast mass found to be invasive ductal carcinoma on core biopsy.
    • No preoperative therapy for the current breast cancer has been started (endocrine therapy, chemotherapy, or radiation). Patients can receive preoperative treatment after TMEM-MRI is conducted, if clinically indicated.

  • For pilot phase Cohort C:

    • Patients with locally advanced breast cancer, anatomic stage II-III, who received neoadjuvant therapy as per standard of care.
    • Residual palpable mass > 1 cm in largest diameter after neoadjuvant therapy.
    • Candidate for breast MRI before definitive surgery.
  • Tumor size/breast mass should be > 1 cm in largest diameter (radiologically).
  • Multifocal disease is allowed, as long as patients meet all eligibility criteria.
  • Age ≥ 18 years.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
  • Willingness to undergo a "research breast MRI".

  • Patient must be able to undergo MRI with gadolinium enhancement.

    • No history of untreatable claustrophobia.
    • No presence of non-MRI compatible metallic objects or metallic objects that, in the opinion of a radiologist, would make MRI a contraindication.
    • No history of sickle cell disease.
    • No contraindication to intravenous contrast administration.
    • No known allergy-like reaction to gadolinium
    • No known or suspected renal impairment. Glomerular Filtration Rate (GFR) should be greater than 30 mL/min/1.73 m2.
  • Weight less than or equal to the MRI table limit.
  • Ability to understand and willingness to sign a written informed consent.

Exclusion Criteria

  • Patients may not have had breast cancer or radiation therapy to the ipsilateral breast in the past.
  • No breast prosthetic implants (silicone or saline) are allowed.
  • Use of any investigational agent within 30 days of starting study.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study.
  • Patients must be non-pregnant and non-lactating. Patients must have a negative pregnancy test (urine or serum) within 7 days of registration date.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Post-biopsy patients (Cohort B)
Patients after breast biopsy. Once consent is obtained, patients will undergo TMEM-MRI. The patients will undergo definitive breast surgery and will receive adjuvant treatments as per NCCN/ASCO guidelines. TMEM density, MenaCalc and MenaINV will be evaluated in final surgical specimen. Uth qTPERM will be correlated with TMEM density, MenaCalc and MenaINV.
Device: TMEM-MRI
TMEM MRI INFORMATION: Unilateral breast MRI will be obtained on a 3.0T whole body MRI scanner with a dedicated breast radiofrequency coil. The patient will be scanned in the prone position with an in-dwelling IV catheter for a single dose contrast agent injection.
Other: Pre-biopsy patients (Cohort A)

Patients identified by radiologist at the time of diagnostic evaluation and TMEM-MRI scheduled. After TMEM-MRI, the patient will undergo core biopsy as per usual radiology procedure, with additional fine-needle aspiration (FNA) preceding the core biopsy). After the breast biopsy confirms the suspected diagnosis of invasive breast carcinoma, the patient will be referred to breast surgery and a treatment plan devised per National Comprehensive Cancer Network/American Society of Clinical Oncology (NCCN/ASCO) guidelines.

No patients were enrolled into this arm/group and Cohort A has been removed by protocol amendment. This was intended to be a cohort for patients before breast biopsy in the event the biopsy procedure created a hematoma which would, in turn, affect measurement of TMEM-MRI activity. Since this effect was not observed in the first set of patients enrolled, Cohort A was removed from the study and only patients post-breast biopsy were enrolled (Cohort B).
Device: TMEM-MRI
TMEM MRI INFORMATION: Unilateral breast MRI will be obtained on a 3.0T whole body MRI scanner with a dedicated breast radiofrequency coil. The patient will be scanned in the prone position with an in-dwelling IV catheter for a single dose contrast agent injection.
Procedure: FNA
FNA: The patients who are recruited prior to biopsy (Cohort A) will have had TMEM-MRI performed prior to biopsy. They will then present to radiology for ultrasound-guided core biopsy of the breast mass. FNA will be performed during this procedure. The FNA will be performed after local anesthetic is administered but prior to insertion of the core biopsy needle. FNA will be performed by the radiologist under direct sonographic visualization of the mass. Five passes will be obtained with a 25-gauge needle. The FNA material will be expelled into 1.5 ml Eppendorf tube containing phosphate buffered saline with Ethylenediaminetetraacetic acid (EDTA).
Other: Post-neoadjuvant therapy patients (Cohort C)
Patients status post neoadjuvant therapy. Patients who received neoadjuvant will be enrolled into Cohort C to understand the correlation between TMEM MRI activity and TMEM doorway density following after neoadjuvant chemotherapy. Only patients with residual palpable mass on physical exam will be included (≥ 1cm). Patients will undergo TMEM-MRI after neoadjuvant therapy is completed. Patients will also have CTCs and circulating tumor DNA (ctDNA) measured on the same day of TMEM-MRI (+/- 3 days). TMEM density, MenaCalc and MenaINV will be evaluated in breast surgical specimen (after pre-operative therapy). Uth qTPERM will be correlated with TMEM density, MenaCalc and MenaINV after pre-operative therapy.
Device: TMEM-MRI
TMEM MRI INFORMATION: Unilateral breast MRI will be obtained on a 3.0T whole body MRI scanner with a dedicated breast radiofrequency coil. The patient will be scanned in the prone position with an in-dwelling IV catheter for a single dose contrast agent injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tumor permeability assessed by TMEM-MRI
Time Frame: Cohort B: ~14 days following breast biopsy and signing of consent. Cohort C: After neoadjuvant therapy and signing of consent and 0-56 days before surgery
Tumor permeability will be assessed by TMEM-MRI, and is defined as a number of Uth units (the number of tumor voxels with permeability density above threshold divided by the number of all tumor voxels) that will be obtained from the permeability map and TMEM-MRI algorithm.
Cohort B: ~14 days following breast biopsy and signing of consent. Cohort C: After neoadjuvant therapy and signing of consent and 0-56 days before surgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Circulating Tumor Cells (CTCs)
Time Frame: Cohort B: ~14 days following breast biopsy and signing of consent. Cohort C: After neoadjuvant therapy and consent and 0-56 days before surgery
CTCs will detected and enumerated from peripheral blood samples using EPIC sciences or RareCyte platform. Patients will undergo venipuncture to obtain specimen for CTC assays. Specimens will be shipped to EPIC sciences (using CTC liquid biopsy blood collection kit) or the University of Southern California (using RareCyte collection kit) to be processed and analyzed as per respective protocols. CTCs will be measured +/- 3 days of TMEM-MRI. Group mean results in number of cells/mL of peripheral blood will be reported for patients in pilot phase Cohort B and pilot phase Cohort C.
Cohort B: ~14 days following breast biopsy and signing of consent. Cohort C: After neoadjuvant therapy and consent and 0-56 days before surgery
TMEM density in breast cancer patients
Time Frame: Cohort B: ~14 days following breast biopsy and consent. Cohort C: After neoadjuvant therapy and signing of consent analyses. Conducted on tissue sections from formalin-fixed paraffin-embedded breast cancer specimen resected for therapeutic purposes
TMEM density is defined as the number of TMEM units visualized by triple immunohistochemistry in 10 high power fields (40X). TMEM density will be measured with a fully automated and scalable clinical assay for identification and enumeration of TMEM utilizing digital pathology methods coupled with image analysis
Cohort B: ~14 days following breast biopsy and consent. Cohort C: After neoadjuvant therapy and signing of consent analyses. Conducted on tissue sections from formalin-fixed paraffin-embedded breast cancer specimen resected for therapeutic purposes
MenaCalc
Time Frame: Cohort B: ~14 days following breast biopsy and consent. Cohort C: After neoadjuvant therapy and signing of consent analyses. Conducted on tissue sections from formalin-fixed paraffin-embedded breast cancer specimen resected for therapeutic purposes
MenaCalc is calculated by subtracting the Z-score value of Mena11a from the Z-score value of pan-Mena, obtained by quantitative immunohistochemistry in formalin-fixed paraffin-embedded breast tumor specimens. MenaCalc can also be measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in cancer cells obtained by FNA
Cohort B: ~14 days following breast biopsy and consent. Cohort C: After neoadjuvant therapy and signing of consent analyses. Conducted on tissue sections from formalin-fixed paraffin-embedded breast cancer specimen resected for therapeutic purposes
MenaInv
Time Frame: Cohort B: ~14 days following breast biopsy and consent. Cohort C: After neoadjuvant therapy and signing of consent analyses. Conducted on tissue sections from formalin-fixed paraffin-embedded breast cancer specimen resected for therapeutic purposes
MenaInv is calculated as pixel intensity obtained by quantitative immunofluorescence per area of formalin-fixed paraffin-embedded tumor tissue. MenaINV can also be measured by qRT-PCR in cancer cells obtained by FNA
Cohort B: ~14 days following breast biopsy and consent. Cohort C: After neoadjuvant therapy and signing of consent analyses. Conducted on tissue sections from formalin-fixed paraffin-embedded breast cancer specimen resected for therapeutic purposes

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Montefiore Medical Center

Collaborators

University of Southern California

Investigators

  • Principal Investigator: Jesus Anampa, MD, MS, Montefiore Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 12, 2018

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

September 28, 2018

First Submitted That Met QC Criteria

October 1, 2018

First Posted (Actual)

October 3, 2018

Study Record Updates

Last Update Posted (Estimated)

November 7, 2025

Last Update Submitted That Met QC Criteria

November 5, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2018-9529

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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